Autologous Mesenchymal Stem Cell (MSC) Transplantation in MS

A Phase I Study to Assess the Feasibility, Safety, and Tolerability of Autologous Mesenchymal Stem Cell Transplantation in Patients With Relapsing Forms of Multiple Sclerosis

The study is an investigator-run, open-label Phase 1 safety study of autologous mesenchymal stem cell transplantation, involving approximately 24 ambulatory participants with relapsing forms of MS (approximately equal numbers with relapsing-remitting and secondary progressive/ progressive relapsing MS) and evidence of involvement of the anterior afferent visual system.

Study Overview

• Status: Completed
• Conditions: Relapsing-Remitting Multiple Sclerosis; Secondary Progressive Multiple Sclerosis; Progressive Relapsing Multiple Sclerosis
• Intervention / Treatment: Biological: Autologous mesenchymal stem cell transplantation

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Mellen Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 to 55, inclusive.
• Diagnosis of MS
• Relapsing form of MS (relapsing-remitting, secondary progressive, or progressive-relapsing course).
• EDSS score 3.0-6.5, inclusive. (Must be able to walk)
• Active disease during prior 24 months.
• Documented evidence of involvement of the anterior afferent visual system: previous optic neuritis, optic atrophy or an afferent pupillary defect on exam, RNFL thickness on OCT <LLN in at least one eye OR documented VEP latency in at least 1 eye.
• Cranial MRI scan demonstrating T2-hyperintense lesions satisfying diagnostic criteria for MS
• Ability to perform the component tests of the MSFC (T25FW, 9HPT, PASAT3).
• Ability to perform SLCLA.
• Has given written informed consent to participate in the study.

Exclusion Criteria:

• A clinically significant infectious illness (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days of the Screening Visit.
• History of cancer other than basal cell carcinoma of the skin.
• History or laboratory results indicative of any significant cardiac, endocrine, hematologic, hepatic, immunologic, infectious, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric, renal, neoplastic, or other disorder that in the opinion of the Principal Investigator would preclude the safe performance of BM aspiration, infusion of autologous MSCs, or performance of any of the planned study assessments.
• Abnormal blood tests which exceed designated limits.
• Positive screening tests for hepatitis B, hepatitis C, HIV 1&2, HTLV I/II, CMV, West Nile virus, syphilis, blood parasite infection.
• Clinically significant abnormality on chest X-ray.
• Clinically significant abnormality on EKG.
• Oxygen-saturation <90% on room air.
• History of alcohol or drug abuse within one year.
• Any metallic material or electronic device in the body, or condition that precludes the participant from undergoing MRI with Gd administration.
• Uncontrolled glaucoma or other ocular condition that precludes performing OCT or interpreting the results.
• MS relapse with onset within 30 days prior to the Screening Visit or the participant has not stabilized from a previous relapse at the time of the Screening Visit.
• Current treatment with an investigational MS disease therapy.
• Prior treatment with:

Total lymphoid irradiation. Cladribine. T-cell or T-cell receptor vaccination. Campath-1h (alemtuzumab). Rituxan (rituximab).

• Prior treatment within three months with:

Tysabri (natalizumab). Gilenya (Fingolimod/FTY720). Zenapax (daclizumab). Cytoxan (cyclophosphamide). Novantrone (mitoxantrone). Cyclosporine. CellCept (mycophenolate mofetil). Imuran (azathioprine). Rheumatrex (methotrexate). IV gamma globulin. Plasma exchange.

• Prior treatment within one month:

Systemic corticosteroids with daily dose equivalent to Prednisone 60 mg or greater.

• Female participants who are not post-menopausal for at least one year, not surgically sterile, or not willing to practice effective contraception.
• Nursing mothers, pregnant women, or women planning to become pregnant during the study.
• Male participants who are not willing to practice effective contraception.
• Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that, in the opinion of the Principal Investigator, is likely to affect the participant's ability to comply with the study protocol.
• Any other reason that, in the opinion of the Principal Investigator, makes the participant unsuitable for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous MSC transplantation	Biological: Autologous mesenchymal stem cell transplantation; A single IV infusion of up to 2 million cells per kg based on the MSC numbers achieved after culture expansion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the feasibility of culturing MSCs, and infusion-related safety and tolerability of autologous MSC transplantation over one month in patients with relapsing forms of MS	1 month

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate effects on MS disease activity measured by the number of Gd-enhancing brain MRI lesions	1 month
To evaluate safety and tolerability of autologous MSC transplantation over 6 months	6 months

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Collaborators: University Hospitals Cleveland Medical Center
• Investigators: Principal Investigator: Jeffrey A Cohen, M.D., The Cleveland Clinic

Publications and helpful links

General Publications

• Cohen JA, Imrey PB, Planchon SM, Bermel RA, Fisher E, Fox RJ, Bar-Or A, Sharp SL, Skaramagas TT, Jagodnik P, Karafa M, Morrison S, Reese Koc J, Gerson SL, Lazarus HM. Pilot trial of intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis. Mult Scler. 2018 Apr;24(4):501-511. doi: 10.1177/1352458517703802. Epub 2017 Apr 6.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: December 22, 2008
• First Submitted That Met QC Criteria: December 22, 2008
• First Posted (Estimate): December 23, 2008

Study Record Updates

• Last Update Posted (Estimate): March 30, 2016
• Last Update Submitted That Met QC Criteria: March 28, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Autologous; MSC; Mesenchymal Stem Cell
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis; Multiple Sclerosis, Relapsing-Remitting
• Other Study ID Numbers: MS-MSC-001